Intensive Diabetes Therapy and Glomerular Filtration Rate in Type 1 Diabetes

T h e n e w e n g l a n d j o u r n a l o f m e d i c i n eoriginal articleIntensive Diabetes Therapy and GlomerularFiltration Rate in Type 1 Diabetes

The DCCT/EDIC Research Group*A B S T R A C T

The members of the writing group for this analysis of the Diabetes Control and Complications Trial (DCCT) and the Epi- demiology of Diabetes Interventions and Complications (EDIC) study (Ian H. de Boer, M.D., University of Washington, Seattle; Wanjie Sun, M.S., Patricia A. Cleary, M.S., and John M. Lachin, Sc.D., The George Washington University, Rock- ville, MD; Mark E. Molitch, M.D., North- western University, Chicago; Michael W. Steffes, M.D., Ph.D., University of Minne- sota, Minneapolis; and Bernard Zinman, M.D., Samuel Lunenfeld Research Insti- tute, Mount Sinai Hospital, University of Toronto, Toronto) assume responsibility for the content and integrity of this article. Address reprint requests to Dr. de Boer at the Kidney Research Institute and Divi- sion of Nephrology, University of Washing- ton, Box 359606, 925 9th Ave, Seattle, WA98104, or at deboer@u.washington.edu.

*A complete list of the participants in the DCCT/EDIC research group is provided in the Supplementary Appendix, avail- able at NEJM.org.

This article (10.1056/NEJMoa1111732) was published on November 12, 2011, at NEJM.org.

N Engl J Med 2011;365:2366-76.

Copyright 2011 Massachusetts Medical Society.

BackgroundAn impaired glomerular f iltration rate (GFR) leads to end-stage renal disease and increases the risks of cardiovascular disease and death. Persons with type 1 diabe- tes are at high risk for kidney disease, but there are no interventions that have been proved to prevent impairment of the GFR in this population.MethodsIn the Diabetes Control and Complications Trial (DCCT), 1441 persons with type 1 diabetes were randomly assigned to 6.5 years of intensive diabetes therapy aimed at achieving near-normal glucose concentrations or to conventional diabetes therapy aimed at preventing hyperglycemic symptoms. Subsequently, 1375 participants were followed in the observational Epidemiology of Diabetes Interventions and Complica- tions (EDIC) study. Serum creatinine levels were measured annually throughout the course of the two studies. The GFR was estimated with the use of the Chronic Kidney Disease Epidemiology Collaboration formula. We analyzed data from the two studies to determine the long-term effects of intensive diabetes therapy on the risk of im- pairment of the GFR, which was defined as an incident estimated GFR of less than60 ml per minute per 1.73 m2 of body-surface area at two consecutive study visits.ResultsOver a median follow-up period of 22 years in the combined studies, impairment of the GFR developed in 24 participants assigned to intensive therapy and in 46 assigned to conventional therapy (risk reduction with intensive therapy, 50%; 95% confidence interval, 18 to 69; P = 0.006). Among these participants, end-stage renal disease de- veloped in 8 participants in the intensive-therapy group and in 16 in the conventional- therapy group. As compared with conventional therapy, intensive therapy was associ- ated with a reduction in the mean estimated GFR of 1.7 ml per minute per 1.73 m2 during the DCCT study but during the EDIC study was associated with a slower rate of reduction in the GFR and an increase in the mean estimated GFR of 2.5 ml per minute per 1.73 m2 (P